Effect of the nano/microscale structure of biomaterial scaffolds on bone regeneration

Abstract

Natural bone is a mineralized biological material, which serves a supportive and protective framework for the body, stores minerals for metabolism, and produces blood cells nourishing the body. Normally, bone has an innate capacity to heal from damage. However, massive bone defects due to traumatic injury, tumor resection, or congenital diseases pose a great challenge to reconstructive surgery. Scaffold-based tissue engineering (TE) is a promising strategy for bone regenerative medicine, because biomaterial scaffolds show advanced mechanical properties and a good degradation profile, as well as the feasibility of controlled release of growth and differentiation factors or immobilizing them on the material surface. Additionally, the defined structure of biomaterial scaffolds, as a kind of mechanical cue, can influence cell behaviors, modulate local microenvironment and control key features at the molecular and cellular levels. Recently, nano/micro-assisted regenerative medicine becomes a promising application of TE for the reconstruction of bone defects. For this reason, it is necessary for us to have in-depth knowledge of the development of novel nano/micro-based biomaterial scaffolds. Thus, we herein review the hierarchical structure of bone, and the potential application of nano/micro technologies to guide the design of novel biomaterial structures for bone repair and regeneration.

References

[1] Liu Y, Luo D, Wang T. Hierarchical structures of bone and bioinspired bone tissue engineering. Small, 2016, 12: 4611-4632.

[2] Wegst UGK, Bai H, Saiz E, Tomsia AP, Ritchie RO. Bioinspired structural materials. Nat. Mater., 2015, 14: 23-36.

[3] Bueno EM, Glowacki J. Cell-free and cell-based approaches for bone regeneration. Nat. Rev. Rheumatol., 2009, 5: 685-697.

[4] Hao Z, . The scaffold microenvironment for stem cell based bone tissue engineering. Biomater. Sci., 2017, 5: 1382-1392.

[5] Reznikov N, Shahar R, Weiner S. Bone hierarchical structure in three dimensions. Acta Biomater., 2014, 10,: 3815-3826.

[6] Zhang C, Mcadams DA, Grunlan JC. Nano/micro-manufacturing of bioinspired materials: a review of methods to mimic matural structures. Adv. Mater., 2016, 28: 6292-6321.

[7] Karageorgiou V, Kaplan D. Porosity of 3D biomaterial scaffolds and osteogenesis. Biomaterials, 2005, 26: 5474-5491.

[8] Iaquinta MR, . Innovative biomaterials for bone regrowth. Int. J. Mol. Sci., 2019, 20: 618.

[9] Ho-Shui-Ling A, . Bone regeneration strategies: engineered scaffolds, bioactive molecules and stem cells current stage and future perspectives. Biomaterials, 2018, 180: 143-162.

[10] Pacelli S, . Strategies to develop endogenous stem cell-recruiting bioactive materials for tissue repair and regeneration. Adv. Drug Deliv. Rev., 2017, 120: 50-70.

[11] Ovsianikov A, Khademhosseini A, Mironov V. The Synergy of scaffold-based and scaffold-free tissue engineering strategies. Trends Biotechnol., 2018, 36: 348-357.

[12] Chen X, . Scaffold structural microenvironmental cues to guide tissue regeneration in bone tissue applications. Nanomaterials, 2018, 8: 960.

[13] Rustom LE, . Micropore-induced capillarity enhances bone distribution in vivo in biphasic calcium phosphate scaffolds. Acta Biomater., 2016, 44: 144-154.

[14] Kaur G, . A review of bioactive glasses: their structure, properties, fabrication and apatite formation. J. Biomed. Mater. Res. A, 2014, 102: 254-274.

[15] Thrivikraman G, Athirasala A, Twohig C, Boda SK, Bertassoni LE. Biomaterials for craniofacial bone regeneration. Dent. Clin. N. Am., 2017, 61: 835-856.

[16] Zhu J, Marchant RE. Design properties of hydrogel tissue-engineering scaffolds. Expert Rev. Med. Devic., 2014, 8: 607-626.

[17] Neves, S. C., Moroni, L., Barrias, C. C. & Granja, P. L. Leveling up hydrogels: hybrid systems in tissue engineering. Trends Biotechnol. pii: S0167-7799(19)30230-6 (2019). https://doi.org/10.1016/j.tibtech.2019.09.004.

[18] Raucci MG, D’Amora U, Ronca A, Demitri C, Ambrosio L. Bioactivation routes of gelatin-based scaffolds to enhance at nanoscale level bone tissue regeneration. Front. Bioeng. Biotechnol., 2019, 7: 27.

[19] Hasan A, . Advances in osteobiologic materials for bone substitutes. J. Tissue Eng. Regen. Med, 2018, 12: 1448-1468.

[20] Kaur G, . Mechanical properties of bioactive glasses, ceramics, glass-ceramics and composites: state-of-the-art review and future challenges. Mater. Sci. Eng. C. Mater. Biol. Appl., 2019, 104: 109895.

[21] Lai Y, . Porous composite scaffold incorporating osteogenic phytomolecule icariin for promoting skeletal regeneration in challenging osteonecrotic bone in rabbits. Biomaterials, 2018, 153: 1-13.

[22] Kim HD, . Biomimetic materials and fabrication approaches for bone tissue engineering. Adv. Healthc. Mater., 2017, 6: 1700612.

[23] Groen N, . Linking the transcriptional landscape of bone induction to biomaterial design parameters. Adv. Mater., 2017, 29: 1603259.

[24] Choi B, Lee S. Nano/micro-assisted regenerative medicine. Int. J. Mol. Sci., 2018, 19: 2187.

[25] Cao L, . Bone regeneration using photocrosslinked hydrogel incorporating rhBMP-2 loaded 2-N, 6-O-sulfated chitosan nanoparticles. Biomaterials, 2014, 35: 2730-2742.

[26] Zhang W, . Magnetically controlled growth-factor-immobilized multilayer cell sheets for complex tissue regeneration. Adv. Mater., 2017, 29: 1703795.

[27] Liu Y, . Thermodynamically controlled self-assembly of hierarchically staggered architecture as an osteoinductive alternative to bone autografts. Adv. Funct. Mater., 2019, 29: 1806445.

[28] Zhou K, . Hierarchically porous hydroxyapatite hybrid scaffold incorporated with reduced graphene oxide for rapid bone ingrowth and repair. ACS Nano, 2019, 13: 9595-9606.

[29] Reznikov N, . Individual response variations in scaffold-guided bone regeneration are determined by independent strain- and injury-induced mechanisms. Biomaterials, 2019, 194: 183-194.

[30] Du Y, Guo JL, Wang J, Mikos AG, Zhang S. Hierarchically designed bone scaffolds: from internal cues to external stimuli. Biomaterials, 2019, 218: 119334.

[31] Chen X, Wang W, Cheng S, Dong B, Li CY. Mimicking bone nanostructure by combining block copolymer self-assembly and 1D crystal nucleation. ACS Nano, 2013, 7: 8251-8257.

[32] Inzana JA, . 3D printing of composite calcium phosphate and collagen scaffolds for bone regeneration. Biomaterials, 2014, 35: 4026-4034.

[33] Xue J, Xie J, Liu W, Xia Y. Electrospun nanofibers: new concepts, materials, and applications. Acc. Chem. Res., 2017, 50: 1976-1987.

[34] Wubneh A, Tsekoura EK, Ayranci C, Uludağ H. Current state of fabrication technologies and materials for bone tissue engineering. Acta Biomater., 2018, 80: 1-30.

[35] Prasad A, Sankar MR, Katiyar V. State of art on solvent casting particulate leaching method for orthopedic scaffolds fabrication. Mater. Today Proc., 2017, 4: 898-907.

[36] Sola A, . Development of solvent-casting particulate leaching (SCPL) polymer scaffolds as improved three-dimensional supports to mimic the bone marrow niche. Mater. Sci. Eng. C. Mater. Biol. Appl., 2019, 96: 153-165.

[37] Kim H, Kim HW, Suh H. Sustained release of ascorbate-2-phosphate and dexamethasone from porous PLGA scaffolds for bone tissue engineering using mesenchymal stem cells. Biomaterials, 2003, 24: 4671-4679.

[38] Thadavirul N, Pavasant P, Supaphol P. Development of polycaprolactone porous scaffolds by combining solvent casting, particulate leaching, and polymer leaching techniques for bone tissue engineering. J. Biomed. Mater. Res. A., 2014, 102: 3379-3392.

[39] Wu F, Wei J, Liu C, Brian O’Neill, Ngothai Y. Fabrication and properties of porous scaffold of zein/PCLl biocomposite for bone tissue engineering. Compos. B Eng., 2012, 43: 2192-2197.

[40] Nam YS, Park TG. Biodegradable polymeric microcellular foams by modified thermally induced phase separation method. Biomaterials, 1999, 20: 1783-1790.

[41] Nam YS, Park TG. Porous biodegradable polymeric scaffolds prepared by thermally induced phase separation. J. Biomed. Mater. Res., 1999, 47: 8-17.

[42] Kim HD. Effect of PEG–PLLA diblock copolymer on macroporous PLLA scaffolds by thermally induced phase separation. Biomaterials, 2004, 25: 2319-2329.

[43] Blaker JJ, Knowles JC, Day RM. Novel fabrication techniques to produce microspheres by thermally induced phase separation for tissue engineering and drug delivery. Acta Biomater., 2008, 4: 264-272.

[44] Lei. B, . Nanofibrous gelatin–silica hybrid scaffolds mimicking the native extracellular matrix (ECM) using thermally induced phase separation. J. Mater. Chem., 2012, 22: 14133-14140.

[45] Sepulveda P, Jones JR, Hench LL. Bioactive sol‐gel foams for tissue repair. J. Biomed. Mater. Res., 2002, 59: 340-348.

[46] Jones JR, Ehrenfried LM, Hench LL. Optimising bioactive glass scaffolds for bone tissue engineering. Biomaterials, 2006, 27: 964-973.

[47] Kaur G, Pickrell G, Sriranganathan N, Kumar V, Homa D. Review and the state of the art: sol–gel and melt quenched bioactive glasses for tissue engineering. J. Biomed. Mater. Res. B Appl. Biomater., 2016, 104: 1248-1275.

[48] Ding Y, . Electrospun polyhydroxybutyrate/poly (ε-caprolactone)/Sol–gel-derived silica hybrid scaffolds with drug releasing function for bone tissue engineering applications. ACS Appl. Mater. Interfaces, 2018, 10: 4540-14548.

[49] Moreira CD, Carvalho SM, Mansur HS, Pereira MM. Thermogelling chitosan–collagen–bioactive glass nanoparticle hybrids as potential injectable systems for tissue engineering. Mater. Sci. Eng. C. Mater. Biol. Appl., 2016, 58: 1207-1216.

[50] Kim TK, Yoon JJ, Lee DS, Park TG. Gas foamed open porous biodegradable polymeric microspheres. Biomaterials, 2006, 27: 152-159.

[51] Poursamar SA, . The effects of crosslinkers on physical, mechanical, and cytotoxic properties of gelatin sponge prepared via in-situ gas foaming method as a tissue engineering scaffold. Mater. Sci. Eng. C. Mater. Biol. Appl., 2016, 63: 1-9.

[52] Costantini M, . Correlation between porous texture and cell seeding efficiency of gas foaming and microfluidic foaming scaffolds. Mater. Sci. Eng. C. Mater. Biol. Appl., 2016, 62: 668-677.

[53] Rnjak-Kovacina J, . Lyophilized silk sponges: a versatile biomaterial platform for soft tissue engineering. ACS Biomater. Sci. Eng., 2015, 1: 260-270.

[54] Madihally SV, Matthew HWT. Porous chitosan scaffolds for tissue engineering. Biomaterials, 1999, 20: 1133-1142.

[55] Clearfield D, Nguyen A, Wei M. Biomimetic multidirectional scaffolds for zonal osteochondral tissue engineering via a lyophilization bonding approach. J. Biomed. Mater. Res. A, 2018, 106: 48-958.

[56] Rajan N, Habermehl J, Coté MF, Doillon CJ, Mantovani D. Preparation of ready-to-use, storable and reconstituted type I collagen from rat tail tendon for tissue engineering applications. Nat. Protoc., 2006, 1: 2753.

[57] Freytes DO, Tullius RS, Valentin JE, Stewart‐Akers AM, Badylak SF. Hydrated versus lyophilized forms of porcine extracellular matrix derived from the urinary bladder. J. Biomed. Mater. Res. A, 2008, 87: 862-872.

[58] Whitesides GM, Mathias JP, Seto CT. Molecular self-assembly and nanochemistry: a chemical strategy for the synthesis of nanostructures. Science, 1991, 254: 1312-1319.

[59] Li L, . Hierarchical structure and mechanical improvement of an n-HA/GCO–PU composite scaffold for bone regeneration. ACS Appl. Mater. Inter., 2015, 7: 22618-22629.

[60] Farokhi M, . Silk fibroin/hydroxyapatite composites for bone tissue engineering. Biotechnol. Adv., 2018, 36: 68-91.

[61] Quinlan E, . Hypoxia-mimicking bioactive glass/collagen glycosaminoglycan composite scaffolds to enhance angiogenesis and bone repair. Biomaterials, 2015, 52: 358-366.

[62] O’Brien F. Influence of freezing rate on pore structure in freeze-dried collagen-GAG scaffolds. Biomaterials, 2004, 25: 1077-1086.

[63] Quinlan E, Thompson EM, Matsiko A, O’Brien FJ, López-Noriega A. Functionalization of a collagen-hydroxyapatite scaffold with osteostatin to facilitate enhanced bone regeneration. Adv. Healthc. Mater., 2015, 4: 2649-2656.

[64] Cunniffe GM, Dickson GR, Partap S, Stanton KT, O Brien FJ. Development and characterisation of a collagen nano-hydroxyapatite composite scaffold for bone tissue engineering. J. Mater. Sci.: Mater. Med., 2010, 21: 2293-2298.

[65] Jin SS, . A biomimetic hierarchical nanointerface orchestrates macrophage polarization and mesenchymal stem cell recruitment to promote endogenous bone regeneration. ACS Nano, 2019, 13: 6581-6595.

[66] Liu Y, . Hierarchically staggered nanostructure of mineralized collagen as a bone-grafting scaffold. Adv. Mater., 2016, 28: 8740-8748.

[67] Parra-Cabrera C, Achille C, Kuhn S, Ameloot R. 3D printing in chemical engineering and catalytic technology: structured catalysts, mixers and reactors. Chem. Soc. Rev., 2018, 47: 209-230.

[68] Kang H, . A 3D bioprinting system to produce human-scale tissue constructs with structural integrity. Nat. Biotechnol., 2016, 34: 312-319.

[69] Studart AR. Additive manufacturing of biologically-inspired materials. Chem. Soc. Rev., 2016, 45: 359-376.

[70] Kim K, Yeatts A, Dean D, Fisher JP. Stereolithographic bone scaffold design parameters: osteogenic differentiation and signal expression. Tissue Eng. Part. B Rev., 2010, 16: 523-539.

[71] Naghieh S, Ravari MK, Badrossamay M, Foroozmehr E, Kadkhodaei M. Numerical investigation of the mechanical properties of the additive manufactured bone scaffolds fabricated by FDM: the effect of layer penetration and post-heating. J. Mech. Behav. Biomed. Mater., 2016, 59: 241-250.

[72] Liu D, Zhuang J, Shuai C, Peng S. Mechanical properties’ improvement of a tricalcium phosphate scaffold with poly-l-lactic acid in selective laser sintering. Biofabrication, 2013, 5: 025005.

[73] Brunello G, . Powder-based 3D printing for bone tissue engineering. Biotechnol. Adv., 2016, 34: 740-753.

[74] Zocca A, . 3D-printed silicate porous bioceramics using a non-sacrificial preceramic polymer binder. Biofabrication, 2015, 7: 25008.

[75] Liu W, . Low-temperature deposition manufacturing: a novel and promising rapid prototyping technology for the fabrication of tissue-engineered scaffold. Mater. Sci. Eng.: C, 2017, 70: 976-982.

[76] Xu M, . Fabricating a pearl/PLGA composite scaffold by the low-temperature deposition manufacturing technique for bone tissue engineering. Biofabrication, 2010, 2: 25002.

[77] Lee M, Dunn JC, Wu BM. Scaffold fabrication by indirect three-dimensional printing. Biomaterials, 2005, 26: 4281-4289.

[78] Daly AC, . 3D bioprinting for cartilage and osteochondral tissue engineering. Adv. Healthc. Mater., 2017, 6: 1700298.

[79] Sears N, Dhavalikar P, Whitely M, Cosgriff-Hernandez E. Fabrication of biomimetic bone grafts with multi-material 3D printing. Biofabrication, 2017, 9: 25020.

[80] Murphy SV, Atala A. 3D bioprinting of tissues and organs. Nat. Biotechnol., 2014, 32: 773.

[81] Rider P, Kačarević ŽP, Alkildani S, Retnasingh S, Barbeck M. Bioprinting of tissue engineering scaffolds. J. Tissue Eng., 2018, 9: 2041731418802090.

[82] Gurkan UA, . Engineering anisotropic biomimetic fibrocartilage microenvironment by bioprinting mesenchymal stem cells in nanoliter gel droplets. Mol. Pharm., 2014, 11: 2151-2159.

[83] Wang MO, . Evaluating 3D-printed biomaterials as scaffolds for vascularized bone tissue engineering. Adv. Mater., 2015, 27: 138-144.

[84] Yao Q, . Three dimensional electrospun PCL/PLA blend nanofibrous scaffolds with significantly improved stem cells osteogenic differentiation and cranial bone formation. Biomaterials, 2017, 115: 115-127.

[85] Dhand C, . Bio-inspired in situ crosslinking and mineralization of electrospun collagen scaffolds for bone tissue engineering. Biomaterials, 2016, 104: 323-338.

[86] Moradi SL, Golchin A, Hajishafieeha Z, Khani M, Ardeshirylajimi A. Bone tissue engineering: adult stem cells in combination with electrospun nanofibrous scaffolds. J. Cell. Physiol., 2018, 233: 6509-6522.

[87] Xie J, . Osteogenic differentiation and bone regeneration of iPSC-MSCs supported by a biomimetic nanofibrous scaffold. Acta Biomater., 2016, 29: 365-379.

[88] Zigdon Giladi H, Khutaba A, Elimelech R, Machtei EE, Srouji S. VEGF release from a polymeric nanofiber scaffold for improved angiogenesis. J. Biomed. Mater. Res. A, 2017, 105: 2712-2721.

[89] Li L, . Controlled dual delivery of BMP-2 and dexamethasone by nanoparticle-embedded electrospun nanofibers for the efficient repair of critical-sized rat calvarial defect. Biomaterials, 2015, 37: 218-229.

[90] Sola A, Bellucci D, Cannillo V. Functionally graded materials for orthopedic applications – an update on design and manufacturing. Biotechnol. Adv., 2016, 34: 504-531.

[91] Reznikov N, Bilton M, Lari L, Stevens MM, Kröger R. Fractal-like hierarchical organization of bone begins at the nanoscale. Science, 2018, 360: 6388.

[92] Stevens MM, George JH. Exploring and engineering the cell surface interface. Science, 2005, 310: 1135-1138.

[93] Murphy WL, Mcdevitt TC, Engler AJ. Materials as stem cell regulators. Nat. Mater., 2014, 13: 547-557.

[94] Dalby MJ, . The control of human mesenchymal cell differentiation using nanoscale symmetry and disorder. Nat. Mater., 2007, 6: 997-1003.

[95] Hou S, . Simultaneous nano- and microscale structural control of injectable hydrogels via the assembly of nanofibrous protein microparticles for tissue regeneration. Biomaterials, 2019, 223: 119458.

[96] Dalby MJ, Gadegaard N, Oreffo ROC. Harnessing nanotopography and integrin–matrix interactions to influence stem cell fate. Nat. Mater., 2014, 13: 558-569.

[97] Huang G, . Functional and biomimetic materials for engineering of the three-dimensional cell microenvironment. Chem. Rev., 2017, 117: 12764-12850.

[98] Mohiuddin M, Pan H-A, Hung Y-C, Huang GS. Control of growth and inflammatory response of macrophages and foam cells with nanotopography. Nanoscale Res. Lett., 2012, 7: 394-394.

[99] Christo SN, . The role of surface nanotopography and chemistry on primary neutrophil and macrophage cellular responses. Adv. Healthc. Mater., 2016, 5: 956-965.

[100] Sadowska JM, . Effect of nano-structural properties of biomimetic hydroxyapatite on osteoimmunomodulation. Biomaterials, 2018, 181: 318-332.

[101] Chen Z, . Tuning chemistry and topography of nanoengineered surfaces to manipulate immune response for bone regeneration applications. ACS Nano., 2017, 23: 4494-4506.

[102] Sun J, . Intrafibrillar silicified collagen scaffold modulates monocyte to promote cell homing, angiogenesis and bone regeneration. Biomaterials, 2017, 113: 203-216.

[103] Niu LN, . Intrafibrillar silicification of collagen scaffolds for sustained release of stem cell homing chemokine in hard tissue regeneration. FASEB J., 2012, 26: 4517-4529.

[104] Crowder SW, Leonardo V, Whittaker T, Papathanasiou P, Stevens MM. Material cues as potent regulators of epigenetics and stem cell function. Cell Stem Cell, 2016, 18: 39-52.

[105] Gilchrist CL, Ruch DS, Little D, Guilak F. Micro-scale and meso-scale architectural cues cooperate and compete to direct aligned tissue formation. Biomaterials, 2014, 35: 10015-10024.

[106] Maleki H, . Mechanically strong silica-silk fibroin bioaerogel: a hybrid scaffold with ordered honeycomb micromorphology and multiscale porosity for bone regeneration. ACS Appl. Mater. Inter., 2019, 11: 17256-17269.

[107] Barba A, . Osteogenesis by foamed and 3D-printed nanostructured calcium phosphate scaffolds: effect of pore architecture. Acta Biomater., 2018, 79: 135-147.

[108] Huebsch N, . Matrix elasticity of void-forming hydrogels controls transplanted-stem-cell-mediated bone formation. Nat. Mater., 2015, 14: 1269-1277.

[109] Gupte MJ, . Pore size directs bone marrow stromal cell fate and tissue regeneration in nanofibrous macroporous scaffolds by mediating vascularization. Acta Biomater., 2018, 82: 1-11.

[110] Preethi SS, Haritha MA, Viji CS, Selvamurugan N. Bone tissue engineering: scaffold preparation using chitosan and other biomaterials with different design and fabrication techniques. Int. J. Biol. Macromol., 2018, 119: 1228-1239.

[111] Mitra D, Whitehead J, Yasui OW, Leach JK. Bioreactor culture duration of engineered constructs influences bone formation by mesenchymal stem cells. Biomaterials, 2017, 146: 29-39.

[112] Dutta RC, Dey M, Dutta AK, Basu B. Competent processing techniques for scaffolds in tissue engineering. Biotechnol. Adv., 2017, 35: 240-250.

[113] Viswanathan P, . 3D surface topology guides stem cell adhesion and differentiation. Biomaterials, 2015, 52: 140-147.

[114] Petersen, A. et al. A biomaterial with a channel-like pore architecture induces endochondral healing of bone defects. Nat. Commun. 9, 4430 (2018).

[115] Kim J, Lim J, Naren R, Yun H, Park EK. Effect of the biodegradation rate controlled by pore structures in magnesium phosphate ceramic scaffolds on bone tissue regeneration in vivo. Acta Biomater., 2016, 44: 155-167.

[116] Chen Z, . Nanoporous microstructures mediate osteogenesis by modulating the osteo-immune response of macrophages. Nanoscale, 2017, 9: 706-718.

[117] Dinoro J, . Sulfated polysaccharide-based scaffolds for orthopaedic tissue engineering. Biomaterials, 2019, 214: 119214.

[118] Griffin MF, . Chemical group-dependent plasma polymerisation preferentially directs adipose stem cell differentiation towards osteogenic or chondrogenic lineages. Acta Biomater., 2017, 50: 450-461.

[119] Samorezov JE, Alsberg E. Spatial regulation of controlled bioactive factor delivery for bone tissue engineering. Adv. Drug Deliv. Rev., 2015, 84: 45-67.

[120] Bouyer M, . Surface delivery of tunable doses of BMP-2 from an adaptable polymeric scaffold induces volumetric bone regeneration. Biomaterials, 2016, 104: 168-181.

[121] Autefage H, . Multiscale analyses reveal native-like lamellar bone repair and near perfect bone-contact with porous strontium-loaded bioactive glass. Biomaterials, 2019, 209: 152-162.

[122] Amir Afshar H, Ghaee A. Preparation of aminated chitosan/alginate scaffold containing halloysite nanotubes with improved cell attachment. Carbohyd. Polym., 2016, 151: 1120-1131.

[123] Orgaz F, . Surface nitridation improves bone cell response to melt-derived bioactive silicate/borosilicate glass composite scaffolds. Acta Biomater., 2016, 29: 424-434.

[124] Yu T, . Influence of surface chemistry on adhesion and osteo/odontogenic differentiation of dental pulp stem cells. ACS Biomater. Sci. Eng., 2017, 3: 1119-1128.

[125] Zamani Y, . Enhanced osteogenic activity by MC3T3-E1 pre-osteoblasts on chemically surface-modified poly(epsilon-caprolactone) 3D-printed scaffolds compared to RGD immobilized scaffolds. Biomed. Mater., 2018, 14: 15008.

[126] Neffe AT, . One step creation of multifunctional 3D architectured hydrogels inducing bone regeneration. Adv. Mater., 2015, 27: 1738-1744.

[127] Rather HA, Jhala D, Vasita R. Dual functional approaches for osteogenesis coupled angiogenesis in bone tissue engineering. Mater. Sci. Eng.: C, 2019, 103: 109761.

[128] Tamburaci S, Tihminlioglu F. Biosilica incorporated 3D porous scaffolds for bone tissue engineering applications. Mater. Sci. Eng.: C, 2018, 91: 274-291.

[129] Shkarina S, . 3D biodegradable scaffolds of polycaprolactone with silisilicate-containing hydroxyapatite microparticles for bone tissue engineering: high-resolution tomography and in vitro study. Sci. Rep., 2018, 8

[130] Dinescu S, Ionita M, Ignat S, Costache M, Hermenean A. Graphene oxide enhances chitosan-based 3D scaffold properties for bone tissue engineering. Int. J. Mol. Sci., 2019, 20: 5077.

[131] Xia Y, . Novel magnetic calcium phosphate-stem cell construct with magnetic field enhances osteogenic differentiation and bone tissue engineering. Mater. Sci. Eng. C Mater. Biol. Appl., 2019, 98: 30-41.

[132] Minardi S, . Evaluation of the osteoinductive potential of a bio-inspired scaffold mimicking the osteogenic niche for bone augmentation. Biomaterials, 2015, 62: 128-137.

[133] Zhang J, . Magnesium modification of a calcium phosphate cement alters bone marrow stromal cell behavior via an integrin-mediated mechanism. Biomaterials, 2015, 53: 251-264.

[134] Ryan EJ, . Collagen scaffolds functionalised with copper-eluting bioactive glass reduce infection and enhance osteogenesis and angiogenesis both in vitro and in vivo. Biomaterials, 2019, 197: 405-416.

[135] Dittler ML, . Bioactive glass (45S5)-based 3D scaffolds coated with magnesium and zinc-loaded hydroxyapatite nanoparticles for tissue engineering applications. Colloids Surf. B: Biointerfaces, 2019, 182: 110346.

[136] Liu W, . Zinc-modified sulfonated polyetheretherketone surface with immunomodulatory function for guiding cell fate and bone regeneration. Adv. Sci., 2018, 5: 1800749.

[137] Chen Z, . Osteoimmunomodulatory properties of magnesium scaffolds coated with β-tricalcium phosphate. Biomaterials, 2014, 35: 8553-8565.

[138] Habibovic P, Barralet JE. Bioinorganics and biomaterials: bone repair. Acta Biomater., 2011, 7: 3013-3026.

[139] Zhang W, . Strontium-substituted submicrometer bioactive glasses modulate macrophage responses for improved bone regeneration. ACS Appl Mater. Interfaces, 2016, 8: 30747-30758.

[140] Yu W, . Strontium-doped amorphous calcium phosphate porous microspheres synthesized through a microwave-hydrothermal method using fructose 1,6-bisphosphate as an organic phosphorus source: application in drug delivery and enhanced bone regeneration. ACS Appl. Mater. Interfaces, 2017, 9: 3306-3317.

[141] Yuan X, . Immunomodulatory effects of calcium and strontium co-doped titanium oxides on osteogenesis. Front. Immunol., 2017, 8: 1196.

[142] Niu Y, . Modulating the phenotype of host macrophages to enhance osteogenesis in MSC-laden hydrogels: Design of a glucomannan coating material. Biomaterials, 2017, 139: 39-55.

[143] Peng B, Chen Y, Leong KW. MicroRNA delivery for regenerative medicine. Adv. Drug Deliv. Rev., 2015, 88: 108-122.

[144] Lei L, . Injectable colloidal hydrogel with mesoporous silica nanoparticles for sustained co-release of microRNA-222 and aspirin to achieve innervated bone regeneration in rat mandibular defects. J. Mater. Chem. B, 2019, 7: 2722-2735.

[145] Wang X, Wang G, Zingales S, Zhao B. Biomaterials enabled cell-free strategies for endogenous bone regeneration. Tissue Eng. Part B Rev., 2018, 24: 463-481.

[146] Kim IG, . Bioactive cell-derived matrices combined with polymer mesh scaffold for osteogenesis and bone healing. Biomaterials, 2015, 50: 75-86.

[147] Lin D, . Rapid initiation of guided bone regeneration driven by spatiotemporal delivery of IL-8 and BMP-2 from hierarchical MBG-based scaffold. Biomaterials, 2019, 196: 122-137.

[148] Kuttappan S, . Dual release of growth factor from nanocomposite fibrous scaffold promotes vascularisation and bone regeneration in rat critical sized calvarial defect. Acta Biomater., 2018, 78: 36-47.

Funding

National Natural Science Foundation of China (National Science Foundation of China)(81571815, 81871492, 51902344)

Natural Science Foundation of Beijing Municipality (Beijing Natural Science Foundation)(L182005, 2184119)

Beijing Nova Program(Z171100001117018)

Beijing Nova Programme Interdisciplinary Cooperation Project No. Z181100006218135

Science Foundation of China University of Petroleum, Beijing(2462018BJB002)